The prior art describes the use of prostaglandin analogs containing a ring structure in the omega chain for reducing intraocular pressure. A representative patent in this area is U.S. Pat. No. 5,321,128 to Stjernschantz. These compounds contain a hydroxy group or keto group as a substituent at the 15-position. Also, one subset of these compounds contains an unsubstituted phenyl group substituted on carbon atom number 17 of the omega chain and the absence of carbons 18-20. These types of structures, where the conventional prostaglandin carbons 18-20 and their equivalent are absent are named by Stjernschantz as 18,19,20-trinor prostaglandins.
One of the above-described type of compounds, latanoprost, is now sold commercially as an IOP (intraocular pressure) reducing eye drop. The clinical dosage is 1.5 xcexcg per dose as an eye drop, once a day. This is the U.S. FDA approved dosage. The provided liquid composition product can contain 0.005% latanoprost used at a dosage of one drop, or about 30 xcexcl, providing 1.5 xcexcg per dose. Latanoprost is named by Stjernschantz as 13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2xcex1 isopropyl ester.
Another compound of this family known to date is 13,14-dihydro-15-oxo-17-phenyl-18,19,20-trinor PGF2xcex1 isopropyl ester, hereinafter referred to as 15-keto latanoprost.
The above noted patent describes a wide potential dosage range as therapeutically active. For example, see column 5, lines 33-66 of the ""128 patent (xe2x80x9cThe composition contains about 0.1-30 xcexcg, especially 1-10 xcexcg, per application of the active substance . . . xe2x80x9d). Even so, the lowest dosage used in the ""128 patent for any test compound for evaluating IOP reduction in humans or monkeys is 1.0 xcexcg per eye. For 15-keto latanoprost in the ""128 patent, the tested dosage in healthy human volunteers is 5 xcexcg per eye and is 3 xcexcg in the monkey eye. Latanoprost is tested in the ""128 patent at a dosage of 1.0 xcexcg per eye in healthy human volunteers and at a dosage of 10.4 xcexcg in the monkey eye.
Latanoprost at its clinical concentration can cause pigmentation of the iris, a mild IOP spike and/or mild hyperemia.
It has been discovered that 15-keto latanoprost can be used in an unusually low dosage for reduction of IOP. Another embodiment of the present invention is the use of 15-keto latanoprost at a dosage up to about the clinical dosage of latanoprost. 15-keto latanoprost does not cause iridic pigmentation, an initial IOP spike nor any hyperemia at the dosages described herein. Still another embodiment of the present invention is the use of 15-keto latanoprost for maintaining IOP reduction over an extended time following an initial rapid IOP reduction bought about by another IOP reducing agent, such as latanoprost.
The embodiments of the present invention involve treatment of glaucoma where IOP reduction is needed and the lowering of IOP for purposes other than treatment of glaucoma.
This application describes other 15-keto prostaglandins useable at low dosages for treating ocular hypertension and glaucoma.